Abstract: Objective: To study the vulnerability of astrocytes bearing mutant SOD1 to the oxidative stress. Methods: The cytotoxicity of the serum deprived astrocytes was measured by MTT. The level of ROS was analyzed by the fluorescence of DCF by using confocal microscope. The expression of Nrf2, HO1 and NQO1 in the different cells was detected by the Western blot. Results: The level of cellular toxicity was higher in the astrocytes bearing mutant SOD1 exposed to the oxidative stress than the astrocytes bearing wild type SOD1. In the astrocytes bearing mutant SOD1, the expression of Nrf2, HO1 and NQO1 decreased. In the presence of mutant SOD1, an unexpected 44 percent decreased in the level of Nrf2 was detected. This was associated with decreases in multiple downstream phase II detoxifying enzymes and antioxidant enzymes, known as NQO1 and HO1. Furthermore, our results showed that the expression of NQO1 increased 1.5 and 2.5-fold by EGCG at 5 and 10?mol/L. EGCG also elevated the expression of total Nrf2. Confocal microscopy showed that EGCG caused Nrf2 translocation from the cytoplasm to the nucleus. Conclusions: Decrese in Nrf2 expression is the mechanism underlie the vulnerability of astrocytes bearing mutant SOD1 and EGCG strengthened the ability of antioxidation by upregulating the activity of Nrf2.

Key words: astrocytes, oxidative stress, EGCG